Self-lubricating medical articles

ABSTRACT

Medical articles formed from a polyurethane-based resin including a modifying oligomer provide enhanced properties. A modifying oligomer incorporated into a backbone, as a side chain, or both of the polyurethane-based resin formed by a diisocyanate, a polyglycol, and a diol chain extender has at least one, preferably two, alcohol moieties (C—OH) and a functional moiety. Exemplary modifying oligomers are: a diol-containing perfluoropolyether incorporated into the backbone, a monofunctional polysiloxane (e.g., monodialcohol-terminated polydimethylsiloxane) incorporated as the side chain, and combinations thereof. Medical articles herein are self-lubricating and/or anti-fouling.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. § 119(e) to U.S.Provisional Application No. 62/735,332, filed Sep. 24, 2018, thedisclosure of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

The present disclosure relates to a polyurethane-based resin including abackbone of a diisocyanate, a polyglycol, and a diol chain extender,which also includes addition of at least one modifier to the backbone oras a side chain that enhances the resin characteristics. The modifier isa modifying oligomer that has at least one, preferably two, alcoholmoieties (C—OH) and a functional moiety. The functional moiety may be,for example, a fluoroether or a silicone. One improved characteristic isphase separation, which concentrates a soft segment of the resin towardsa surface of a medical article formed therefrom. The resulting surfaceof the medical article provides advantages including beingself-lubricating and/or anti-fouling, which eliminates a need toseparately provide functional coatings such as a lubricant and/or ananti-fouling agent.

BACKGROUND

Infusion therapy medical devices, such as syringe cannulas and cathetersused for sampling or medicament administration, typically havecomponents that are in sliding contact during use. Such devices requirelubrication of the moving components and may also require lubrication ofan external surface. Many medical devices are fabricated from polymericmaterials that are inherently non-lubricious and require separateapplication of a lubricant to their surfaces for use. Examples ofstate-of-art surface lubrication technologies include silicone surfacecoating, fluorocarbon surface coating, and hydrophilicpolyvinylpyrrolidone (PVP) surface coating.

Catheter-related bloodstream infections may be caused by colonization ofmicroorganisms, which can occur in patients whose treatment includesintravascular catheters and I.V. access devices. These infections canlead to illness and excess medical costs. Impregnating catheters withvarious antimicrobial agents is one approach that has been implementedto prevent these infections. Another approach is surface modificationtechnologies including direct antimicrobial agent (e.g., chlorhexidine)surface coating and coating of water insoluble quaternary ammonium salts(e.g., tridodecylmethyl ammonium chloride) as a binding agent toassociate with antimicrobial agents (e.g., sodium dicloxacillin).

Some blood contact devices have the potential to generate thrombus. Whenblood contacts a foreign material, a complex series of events occur.These involve protein deposition, cellular adhesion and aggregation, andactivation of blood coagulation schemes. Thrombogenicity hasconventionally been counteracted by the use of anticoagulants such asheparin. Attachment of heparin to otherwise thrombogenic polymericsurfaces may be achieved with a coating of water insoluble quaternaryammonium salts (e.g., tridodecylmethyl ammonium chloride) onto polymersubstrate surface as a binding agent to associate with heparin andsynthesis of a polymer substrate containing tertiary amino functionalgroups to be able to bind heparin.

Surface modification technology to apply lubricious, antimicrobial,and/or non-thrombogenic coating onto a medical device surface involvesseveral issues related to the coating technique: (i) the extra step ofpost-coating for surface modification complicates the medical devicemanufacturing process and increases cost and (ii) aqueous or organicsolvents are required in the coating process. When aqueous solution canbe used, it means that the coating composition is water-soluble, whichwill lose its integrity in human body environment. If strong polarorganic solvent has to be used, the solvent can attack the polymersubstrate material and deteriorate the mechanical strength of theoverall medical device. In addition, organic solvent usage isdisadvantageous with respect to environmental, health, and safety inmedical device manufacturing process. Another issue with externalcoatings is migration and/or leakage of active lubricious, antimicrobialand/or non-thrombogenic agent, and the medical device could lose itsadvantageous properties over time.

Elimination of secondary coating steps has advantages in reducing costsof manufacture. In addition, secondary raw materials such as solventsand coating agents can be eliminated, which reduces costs, leads toenvironmental benefits, and improves work-place safety.

Thus, there is a need for polymeric resins, in particular polyurethaneresins, that can provide self-lubricating and/or self-anti-foulingcharacteristics while allowing for tailorability without additives or anextra coating.

SUMMARY

Provided are medical articles, for example, catheter tubing.Non-limiting examples of catheter tubing include: peripheral intravenous(IV) catheters; intravascular catheters; central venous cathetersincluding tri-lumen, bi-lumen, and single lumen; and urinary catheters.Vascular access devices may use catheter tubing as disclosed herein inconjunction with one or more components such as needles and/orguidewires.

Various embodiments are listed below. It will be understood that theembodiments listed below may be combined not only as listed below, butin other suitable combinations in accordance with the scope of theinvention.

In an aspect, a medical article is formed from a polyurethane-basedresin, which is a reaction product of the following ingredients: adiisocyanate; a diol chain extender; a polyglycol; and a modifyingoligomer incorporated into a backbone, as a side chain, or both of thepolyurethane-based resin formed by the diisocyanate, the polyglycol, andthe diol chain extender, the modifying oligomer having an alcohol (C—OH)moiety and a functional moiety. A hard segment content is in the rangeof from 25% to 75% by weight and a soft segment content of the resin isin the range of from 75% to 25% by weight; and the medical article iseffective as a self-lubricating and/or self-anti-fouling medicalarticle.

A concentration of the modifying oligomer of the polyurethane-basedresin at a surface of the medical article may be higher than atheoretical concentration based on uniform distribution of ingredientsof the polyurethane-based resin.

In one or more embodiments, the functional moiety comprises afluoroether, a silicone, or a combination thereof.

The modifying oligomer may be selected from the group consisting of: adiol-containing perfluoropolyether incorporated into the backbone, amonofunctional polysiloxane incorporated as the side chain, andcombinations thereof.

The modifying oligomer may be present in an amount ranging from about0.1 to about 10 weight percent of the overall composition of thepolyurethane-based resin.

In an aspect, a medical article is formed from a polyurethane-basedresin, which is a reaction product of the following ingredients: adiisocyanate; a diol chain extender; a polyglycol; and a modifyingoligomer incorporated into a backbone, as a side chain, or both of thepolyurethane-based resin formed by the diisocyanate, the polyglycol, andthe diol chain extender. A hard segment content is in the range of from25% to 75% by weight and a soft segment content of the resin is in therange of from 75% to 25% by weight; and the medical article has acontact angle with water that is 90° or greater.

In one or more embodiments, the modifying oligomer has an alcohol (C—OH)moiety and a functional moiety.

In one or more embodiments, the functional moiety comprises afluoroether, a silicone, or a combination thereof.

The modifying oligomer may be selected from the group consisting of: adiol-containing perfluoropolyether incorporated into the backbone, amonofunctional polysiloxane incorporated as the side chain, andcombinations thereof.

A concentration of the modifying oligomer of the polyurethane-basedresin at a surface of the medical article may be higher than atheoretical concentration based on uniform distribution of ingredientsof the polyurethane-based resin.

A medical article of any embodiment herein may comprise a coefficient ofstatic friction that is 0.28 or less.

A medical article of any embodiment herein may comprise a water sorptionof 2.2% by weight or less.

A medical article of any embodiment herein may be non-hydratable.

A medical article of any embodiment herein may be effective to reducebacterial biofilm colony formation.

A medical article of any embodiment herein may be effective to reducethrombosis formation.

Another aspect is a method of infusion therapy comprising: infusing amaterial from a medical article according to any embodiment into apatient.

The method may be conducted in the presence or absence of a separatelubricant coated on the medical article.

The method may be conducted in the presence or absence of a separateanti-fouling agent coated on the medical article.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a thermogravimetric analysis (TGA) curve, weight (%) versustemperature (° C.) for an embodiment;

FIG. 2 is a Differential Scanning Calorimetry (DSC) scan of Cycle 1 andCycle 2, heat flow (W/g) versus temperature (° C.) for an embodiment;

FIG. 3 is a Differential Scanning Calorimetry (DSC) scan of Cycle 3,heat flow (W/g) versus temperature (° C.) for an embodiment;

FIG. 4 is a schematic drawing of a chamber used for biofilm formation;and

FIGS. 5-6 are annotated photographs showing thrombosis formationcomparison among PU tubing materials according to embodiments hereinversus a reference.

DETAILED DESCRIPTION

Before describing several exemplary embodiments of the invention, it isto be understood that the invention is not limited to the details ofconstruction or process steps set forth in the following description.The invention is capable of other embodiments and of being practiced orbeing carried out in various ways.

The following terms shall have, for the purposes of this application,the respective meanings set forth below.

Polyglycols include but are not limited to: polyalkylene glycol,polyester glycol, and polycarbonate glycol. A non-limiting specificexample of polyalkylene glycol is polyether glycol. A polyether glycolis a moderate molecular weight oligomer derived from an alkylene oxide,containing both ether linkages and glycol termination.

A chain extender is a short chain (low molecular weight) branched orunbranched diol, diamine or amino alcohol of up to 10 carbon atoms ormixtures thereof. Such hydroxyl- and/or amine-terminated compounds areused during polymerization to impart desired properties to a polymer.

A modifying oligomer (moderate molecular weight) is a compound thatenhances a basic polyurethane structure of a diisocyanate; a diol chainextender; and a polyglycol. Modifying oligomers, which are differentfrom polyglycols, contain functional moieties (e.g., fluoroether and/orsilicone) that migrate onto the polyurethane surface to render theresulting medical article desirable surface properties. Modifyingoligomers used herein have at least one, preferably two, or more thantwo, alcohol moieties (C—OH). The alcohol moieties may be located alonga backbone of the oligomer. The alcohol moieties may be located at anend of the oligomer. In a detailed embodiment, the oligomer terminateswith an alcohol moiety. In one or more embodiments, the modifyingoligomer excludes compounds having silanol (Si—OH) groups.

Isocyanate index is defined as the molar ratio of the total isocyanategroups in the diisocyanate to the total hydroxyl and/or amino groupspresented in polyols and extenders. In general, the polyurethane becomesharder with an increasing isocyanate index. There is, however, a pointbeyond which the hardness does not increase and the other physicalproperties begin to deteriorate.

Principles and embodiments of the present invention relate generally topolyurethane materials having improved surface properties, and methodsof preparing and using them. Provided are medical articles, for example,catheter tubing, that are self-lubricating and/or anti-fouling, whicheliminates a need to separately provide functional coatings such as alubricant and/or an anti-fouling agent. The articles comprise apolyurethane-based resin that is a reaction product of the followingingredients: a diisocyanate; a diol chain extender; a polyglycol; and amodifier incorporated into a backbone of the polyurethane-based resin oras a side chain. The backbone is formed by the diisocyanate, thepolyglycol, and the diol chain extender. The modifier so incorporatedmay be referred to as a modifying oligomer.

A modifying oligomer for the backbone may be a diol-containingperfluoropolyether (PFPE). A modifying oligomer for the as a side chainmay be a monofunctional polysiloxane (e.g., monodialcohol-terminatedpolydimethylsiloxane).

Combinations of modifying oligomers are also included in thisdisclosure. In an embodiment, a polyurethane-based resin is a reactionproduct of: a diisocyanate; a diol chain extender; a polyglycol; and adiol-containing perfluoropolyether. In an embodiment, apolyurethane-based resin is a reaction product of: a diisocyanate; adiol chain extender; a polyglycol; and a monofunctional polysiloxane(e.g., monodialcohol-terminated polydimethylsiloxane). In an embodiment,a polyurethane-based resin is a reaction product of: a diisocyanate; adiol chain extender; a polyglycol; a diol-containing perfluoropolyether;and a monofunctional polysiloxane (e.g., monodialcohol-terminatedpolydimethylsiloxane).

Polyurethane-based resins disclosed herein have enhanced soft segments.The resins in this disclosure are synthesized by a conventional one-stepcopolymerization process. No catalyst or solvent is required. Thesynthesis can also be achieved by a variety of other synthesistechniques with or without catalyst/solvent understood by those skilledin the art. The copolymerization process is expected to produce a moreuniform polymer system and PFPE-based and/or monodialcohol-terminatedPDMS soft segments are likely to drive polymer chain block phaseseparation with PFPE and/or PDMS moieties migrating onto thepolyurethane surface to render the resulting medical article desirablesurface properties, which are not inherent using coating technology.Through structural and compositional design, the resulting resinspossess inherent lubricious and/or antifouling surface properties formedical device applications, thus no post-coating process is required.

Polyurethanes

Polyurethane materials disclosed herein have enhanced surfaceproperties, which may be tailored to fit different practical needs.Medical devices formed of these polyurethane materials are used tocreate a fluid channel from a medication reservoir to a patient in needthereof, where the fluid channel may be inserted into and in fluidcommunication with vascular vessels, or subcutaneous tissue, where theinvasive medical device comprises any of the polyurethane materials asdescribed herein.

An advantage of these polyurethane materials is that they areself-lubricating and/or anti-fouling.

Thermoplastic polyurethanes (TPUs) suitable for medical devices aretypically synthesized from three basic components, a diisocyanate, apolyglycol, and a chain extender, usually a low molecular weight diol,diamine, amino alcohol or water. If the chain extender is a diol, thepolyurethane consists entirely of urethane linkages. If the extender iswater, amino alcohol or diamine, both urethane and urea linkages arepresent, which results in a polyurethaneurea (PUU). Inclusion of anamine-terminated polyether to the polyurethane synthesis also results ina polyurethaneurea. Device applications for thermoplastic polyurethanesinclude central venous catheters (CVCs), peripherally inserted centralcatheter (PICCs), and peripheral intravenous catheters (PIVCs).

Polyurethane and polyurea chemistries are based on the reactions ofisocyanates with other hydrogen-containing compounds, where isocyanatesare compounds having one or more isocyanate group (—N═C═O). Isocyanatecompounds can be reacted with water (H₂O), alcohols (R—OH), carboxylicacids (R—COOH), amines (R_(x)—NH_((3-x)), ureas (R—NH—CONH₂), and amides(R—CONH₂). Certain polyurethanes may be thermoplastic elastomers (TPE),whereas other compositions may be highly cross-linked.

Thermoplastic polyurethanes comprise two-phases or microdomainsconventionally termed hard segments and soft segments, and as a resultare often referred to as segmented polyurethanes. The hard segments,which are generally of high crystallinity, form by localization of theportions of the polymer molecules which include the diisocyanate andchain extender(s). The soft segments, which are generally eithernon-crystalline or of low crystallinity, form from the polyglycol or theoptional amine-terminated polyether. The hard segment content isdetermined by the weight percent of diisocyanate and chain extender inthe polyurethane composition, and the soft segment content is the weightpercent of polyglycol or polydiamine. The thermoplastic polyurethanesmay be partly crystalline and/or partly elastomeric depending on theratio of hard to soft segments. One of the factors which determine theproperties of the polymer is the ratio of hard and soft segments. Ingeneral, the hard segment contributes to hardness, tensile strength,impact resistance, stiffness and modulus while the soft segmentcontributes to water absorption, elongation, elasticity and softness.

Polyurethane materials may be used as raw materials for catheter tubingvia compounding, extrusion/coextrusion or molding.

A base thermoplastic polyurethane may be produced by the reaction of: adiisocyanate, a diol chain extender, at least one polyglycol,optionally, an amine-terminated polyether, and a modifying oligomer. Thepolyurethane may have a hard segment content between about 25% and about75% by weight, where a hard segment is the portion(s) of the polymermolecules which include the diisocyanate and the extender components,which are generally highly crystalline due to dipole-dipole interactionsand/or hydrogen bonding. In contrast, the soft segments formed from thepolyglycol portions and modifying oligomers between the diisocyanate ofthe polymer chains and generally are either amorphous or only partiallycrystalline due to the characteristics of the polyglycol(s) andmodifying oligomer(s). In an embodiment, the hard segment content may bein the range of about 50% to about 75% and the soft segment content maybe in the range of about 25% to about 50%.

Polymerization of the base polyurethane may be a one-stepcopolymerization process without requiring a catalyst, solvent or otheradditives. The synthesis can also be achieved by a variety of othersynthesis techniques with or without catalyst/solvent understood bythose skilled in the art.

The diisocyanate may be selected from the group consisting of: analiphatic diisocyanate, alicyclic diisocyanate and an aromaticdiisocyanate. In various embodiments, the isocyanate may be selectedfrom the group consisting of: 4,4′-diphenylmethane diisocyanate (MDI),toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), andmethylene-bis(4-cyclohexylisocyanate) (HMDI), and combinations thereof.

The diol chain extender may be selected from the group consisting of:ethylene glycol, 1,3-propylene glycol, 1,4-butanediol, neopentyl glycol,and alicyclic glycols having up to 10 carbon atoms.

The polyglycol may be selected from the group consisting of:polyalkylene glycol, polyester glycol, polycarbonate glycol, andcombinations thereof. In an embodiment, the polyglycol comprises thepolyalkylene glycol. In an embodiment, the polyalkylene glycol comprisesone or both of: a polytetramethylene ether glycol and a polyethyleneglycol.

The polytetramethylene ether glycol may be of any desired molecularweight. The polytetramethylene ether glycol (PTMEG) may be PTMEG250,PTMEG650, PTMEG1000, PTMEG1400, PTMEG1800, PTMEG2000, and PTMEG2900.PTMEG has the formula: HO(CH₂CH₂CH₂CH₂—O—)_(n)H, which may have anaverage value of n in the range of 3 to 40. A blend of two or morePTMEG250, PTMEG650, PTMEG1000, PTMEG1400, PTMEG1800, PTMEG2000, andPTMEG2900 may be used such. A preferred an average molecular weight ofthe combination is less than 1000 Da. In one or more embodiments, thepolyols is a blend of two or more PTMEG having the formula:HO(CH₂CH₂CH₂CH₂—O—)_(n)H, where n has an average value in the range of 3to 40 and an average molecular weight of the combination being less than1000 Da.

A further polyalkylene glycol may be polyethylene glycol (PEG) and/orpolypropylene glycol (PPG). The PEG and/or PPG may be any desiredmolecular weight. In an embodiment, the PEG is: PEG4000. PEG4000 is apolyethylene glycol having an average molecular weight of 4,000 Da.

The polyurethane-based resin may further comprise a polyetheramine.Suitable polyetheramines include but are not limited to amine-terminatedpolyethers having repeating units of ethylene oxide, propylene oxide,tetramethylene oxide or combinations thereof and having an averagemolecular weight in the range of about 230 to 4000. Preferredpolyetheramines have propylene oxide repeating units. Jeffamine® D4000is a specific polyetheramine, a polyoxypropylene diamine, having anaverage molecular weight of about 4000.

The modifying oligomers contain functional moieties (e.g., fluoroetherand/or silicone) that migrate onto the polyurethane surface to renderthe resulting medical article desirable surface properties and have atleast one, preferably two, alcohol moieties (C—OH). In one or moreembodiments, the modifying oligomer excludes compounds having silanol(Si—OH) groups.

A modifying oligomer for the backbone may be a diol-containingperfluoropolyether.

In one or more embodiments, the diol-containing perfluoropolyether hasthe following structure.HO(CH₂CH₂O)_(p)CH₂CF₂O(CF₂CF₂O)_(q)(CF₂O)_(r)CF₂CH₂(OCH₂CH₂)_(p)OH

Wherein total of values for p+q+r are such that the fluorine content ofthe oligomer may be in the range of 55% to 60% by weight and the averagemolecular weight of the oligomer is in the range of 1500 to 2200 g/mol.

An exemplary diol-containing perfluoropolyether may be a commercialproduct sold under the trade name Fluorolink® E10-H, which is adialcohol-terminated, ethoxylated PFPE, with about 1,700 Da averagemolecular weight and about 57% w/w fluorine content.

A modifying oligomer as a side chain may be a monofunctionalpolysiloxane. In one or more embodiments, the monofunctionalpolysiloxane is a monodialcohol-terminated polydimethylsiloxane (PDMS)having the following structure.

Values of s may be in the range of 5 to 200.

Exemplary monodialcohol-terminated polydimethylsiloxanes may be acommercial product sold under the product codes MCR-C61, MCR-C62 andMCR-C63. MCR-C62 has an average molecular weight of 5000 Da (s in rangeof 62-63), MCR-C61 has an average molecular weight of 1000 Da (s inrange of 8-9), and MCR-C63 has an average molecular weight of 15,000 Da(s in range of 197-198). In one or more embodiments, the modifyingoligomer for the as a side chain is MCR-C62.

The polyurethanes described herein may be fabricated into film, tubing,and other forms by conventional thermoplastic fabricating techniquesincluding melt casting, compounding, extrusion/coextrusion, molding,etc. The polyurethane described herein may be used for PICCs, PIVCs, andCVCs. The polymer may have incorporated therein, as desired,conventional stabilizers, additives (e.g., a radiopaque filler), and/orprocessing aids. The amounts of these materials will vary depending uponthe application of the polyurethane, but if present, are typically inamounts so ranging from 0.1 to 50 weight percent of the final compound.

General Procedure for Polyurethane Synthesis

The polyurethanes discussed here were prepared by a one-stepcopolymerization process using a pilot-scale polyurethane (PU)processor. The polyglycol(s), modifying oligomer(s), and chainextender(s) in the total amount of about 7.5 kg were charged into B tank(2.5 gallon full tank capacity with a recycle loop) of the PU processorwith adequate mixing through both a tank agitator and the materialrecycle loop; the diisocyanate (calculated amount to react out B tankpolyol mixture) was charged into A tank (2.5 gallon full tank capacitywith a recycle loop) of the PU processor; during reaction, both B tankand A tank materials were pumped through their individual feeding linesat controlled feed rates to achieve an isocyanate index of 1.0 to 1.1;in one or more embodiments, the isocyanate index is 1.02; both the B andA streams were continuously injected through their respective injectorsinto a 8 cc mixing head with high rotor speed for adequate mixing andpoured into silicone pans; the entire PU processor system, including A/Btanks, fill/feed/recycle/drain lines, injectors and mixing head, wasmaintained at a temperature of 50-90° C. (various zone temperaturecontrols) and the tanks were pulled under vacuum of <100 mmHg duringoperation; the silicone pans filled with PU reactants mixture passedthrough a 150° F. conveyor oven with 10-20 min of curing time to achievecomplete reaction; the resulting white PU slab has a dimension of 7.7in×3.5 in×0.3 in. The PU slabs were subsequently grinded into granulatedforms for downstream compounding and extrusion/coextrusion processes.

The PU granulates/chips can be extruded into ribbon sheets formechanical and surface property characterizations. PU ribbon sheets canbe extruded either from a single copolymer composition or from a blendof two or more different PU compositions. Blending/compounding approachwill allow for quick creation and characterization of new PUcompositions using the already existing PU copolymers. Even though themicro-domain structure and molecular weight distribution may bedifferent using direct copolymerization approach compared toblending/compounding approach, we are expecting comparable mechanicaland surface properties as they have the same overall PU composition. Inone or more embodiments, blending/compounding approach was used forextrusion of certain PU ribbon compositions.

Table I. Exemplary Formulations of Polyurethane Resins with the provisothat the ingredients total 100%.

TABLE I I-A I-B I-C Reactant by weight by weight by weight Diisocyanate24-58% 40-58% 43-51% Total Polyglycol 15-75% 15-50% 25-45% Diol ChainExtender 0.1-18%   9-18% 11-15% Modifying oligomer into 0.1-10% 0.1-10%  0.1-10%  backbone and/or side chain Hard Segment % 25-75%50-75% 55-65%Exemplary Polyurethane-Based Resins

Medical articles are formed from a polyurethane-based resin, which is areaction product of the following ingredients: a diisocyanate; a diolchain extender; a polyglycol; and a modifying oligomer comprising adiol-containing perfluoropolyether and/or a monofunctional polysiloxane,the diol-containing perfluoropolyether being incorporated into abackbone and the monofunctional polysiloxane being incorporated as aside chain of the polyurethane-based resin formed by the diisocyanate,the polyglycol, and the diol chain extender. In one or more embodiments,the polyglycol is one or more polyalkylene glycols, which may compriseone or both of: a polytetramethylene ether glycol and a polyethyleneglycol. The resulting polyurethane-based resins are random copolymersbased on the ingredients. A hard segment content is in the range of from25% to 75% by weight, and a soft segment content of the resin is in therange of from 75% to 25% by weight.

Using the following ingredients, various polymer chain segments (A)-(E)are expected: the diisocyanate comprises 4,4′-diphenylmethanediisocyanate (MDI); the diol chain extender comprises 1,4-butanediol;the polyglycols comprise a polytetramethylene ether glycol (PTMEG) withMW range of 250-2900 Da (n=3-40), and optionally a polyethylene glycolwith MW range of 200 to 8000 Da (m=4-182); the modifying oligomerscomprise a diol-containing perfluoropolyether and/or a monofunctionalpolysiloxane. In one or more embodiments, the polyurethane-based resinsare random copolymers comprising the following chain segments of (A) and(B); optionally (C); and one or both of: (D) and (E).

-   -   wherein n is in the range of 3 to 40;

-   -   wherein m is in the range of 4 to 182;

-   -   wherein the total of p+q+r is such that the fluorine content of        the oligomer is in the range of 55% to 60% by weight and the        average molecular weight of the oligomer is in the range of 1500        to 2200 g/mol;

-   -   wherein s is in the range of 5 to 200.

In one or more embodiments, in the polyurethane-based resin thediisocyanate comprises 4,4′-diphenylmethane diisocyanate (MDI); the diolchain extender comprises 1,4-butanediol; the polyglycol comprises apolytetramethylene ether glycol (PTMEG); and the modifying oligomercomprises a diol-containing perfluoropolyether, thereby resulting in arandom copolymer comprising chain segments of (A), (B), and (D).

In one or more embodiments, in the polyurethane-based resin thediisocyanate comprises 4,4′-diphenylmethane diisocyanate (MDI); the diolchain extender comprises 1,4-butanediol; the polyglycols comprise apolytetramethylene ether glycol (PTMEG) and a polyethylene glycol; andthe modifying oligomer comprises a diol-containing perfluoropolyether,thereby resulting in a random copolymer comprising chain segments of(A), (B), (C), and (D).

In one or more embodiments, in the polyurethane-based resin thediisocyanate comprises 4,4′-diphenylmethane diisocyanate (MDI); the diolchain extender comprises 1,4-butanediol; the polyglycol comprises apolytetramethylene ether glycol (PTMEG); and the modifying oligomercomprises a monodialcohol-terminated polydimethylsiloxane (PDMS),thereby resulting in a random copolymer comprising chain segments of(A), (B), and (E).

In one or more embodiments, in the polyurethane-based resin thediisocyanate comprises 4,4′-diphenylmethane diisocyanate (MDI); the diolchain extender comprises 1,4-butanediol; the polyglycol comprises apolytetramethylene ether glycol (PTMEG); and the modifying oligomerscomprise a diol-containing perfluoropolyether and amonodialcohol-terminated polydimethylsiloxane (PDMS), thereby resultingin a random copolymer comprising chain segments of (A), (B), (D), and(E).

In one or more embodiments, in the polyurethane-based resin thediisocyanate comprises 4,4′-diphenylmethane diisocyanate (MDI); the diolchain extender comprises 1,4-butanediol; the polyglycols comprise apolytetramethylene ether glycol (PTMEG) and a polyethylene glycol; andthe modifying oligomer comprises a monodialcohol-terminatedpolydimethylsiloxane (PDMS), thereby resulting in a random copolymercomprising chain segments of (A), (B), (C), and (E).

In one or more embodiments, in the polyurethane-based resin thediisocyanate comprises 4,4′-diphenylmethane diisocyanate (MDI); the diolchain extender comprises 1,4-butanediol; the polyglycols comprise apolytetramethylene ether glycol (PTMEG) and a polyethylene glycol; andthe modifying oligomers comprise a diol-containing perfluoropolyetherand a monodialcohol-terminated polydimethylsiloxane (PDMS), therebyresulting in a random copolymer comprising chain segments of (A), (B),(C), (D), and (E).

Medical Articles

Medical articles may be any plastic part of a fluid path. Exemplarymedical articles that may be formed by polyurethanes disclosed hereinmay be a component of a catheter; a needle/needleless connector; ortubing. Exemplary devices are: central venous catheters,peripherally-inserted central catheters, and peripheral intravenouscatheters. Catheter tubing can be formed through compounding andextrusion/coextrusion processes. During compounding, granulates ofsynthesized base polyurethanes described herein, and an optionalradiopaque filler are added into a twin-screw compounder simultaneously.The mix ratio can be controlled and adjusted by a gravimetricmultiple-feeder system. The mixed polyurethane melt (conveying throughmultiple heating zones) continuously passes through a die, a quenchtank, and is subsequently cut into regular-sized pellets by apuller-pelletizer. The collected pellets are used to be fed into anextruder/coextruder to form a catheter tube, depending on tubing'sspecific configuration.

EMBODIMENTS

Various embodiments are listed below. It will be understood that theembodiments listed below may be combined with all aspects and otherembodiments in accordance with the scope of the invention.

Embodiment 1

A medical article formed from a polyurethane-based resin, which is areaction product of the following ingredients: a diisocyanate; a diolchain extender; a polyglycol; and a modifying oligomer incorporated intoa backbone, as a side chain, or both of the polyurethane-based resinformed by the diisocyanate, the polyglycol, and the diol chain extender,the modifying oligomer having an alcohol (C—OH) moiety and a functionalmoiety; wherein a hard segment content is in the range of from 25% to75% by weight and a soft segment content of the resin is in the range offrom 75% to 25% by weight; and wherein the medical article is effectiveas a self-lubricating and/or self-anti-fouling medical article.

Embodiment 2

The medical article of embodiment 1, wherein a concentration of themodifying oligomer of the polyurethane-based resin at a surface of themedical article is higher than a theoretical concentration based onuniform distribution of ingredients of the polyurethane-based resin.

Embodiment 3

The medical article of any preceding embodiment, wherein the functionalmoiety comprises a fluoroether, a silicone, or a combination thereof.

Embodiment 4

The medical article of any preceding embodiment, wherein the modifyingoligomer is selected from the group consisting of: a diol-containingperfluoropolyether incorporated into the backbone, a monofunctionalpolysiloxane incorporated as the side chain, and combinations thereof.

Embodiment 5

The medical article of any preceding embodiment, wherein the modifyingoligomer is present in an amount ranging from about 0.1 to about 10weight percent of the overall composition of the polyurethane-basedresin.

Embodiment 6

The medical article of any preceding embodiment, wherein thediisocyanate is selected from the group consisting of: an aliphaticdiisocyanate, alicyclic diisocyanate and an aromatic diisocyanate.

Embodiment 7

The medical article of the preceding embodiment, wherein thediisocyanate is selected from the group consisting of:4,4′-diphenylmethane diisocyanate (MDI), toluene diisocyanate (TDI),isophorone diisocyanate (IPDI), andmethylene-bis(4-cyclohexylisocyanate) (HMDI), and combinations thereof.

Embodiment 8

The medical article of any preceding embodiment, wherein the diol chainextender is selected from the group consisting of: ethylene glycol,1,3-propylene glycol, 1,4-butanediol, neopentyl glycol, and alicyclicglycols having up to 10 carbon atoms.

Embodiment 9

The medical article of any preceding embodiment, wherein the polyglycolis selected from the group consisting of: polyalkylene glycol, polyesterglycol, polycarbonate glycol, and combinations thereof.

Embodiment 10

The medical article of the preceding embodiment, wherein the polyglycolcomprises the polyalkylene glycol.

Embodiment 11

The medical article of the preceding embodiment, wherein thepolyalkylene glycol comprises one or both of: a polytetramethylene etherglycol and a polyethylene glycol.

Embodiment 12

The medical article of the preceding embodiment, wherein thepolyalkylene glycol comprises a polytetramethylene ether glycol, and apolyethylene glycol that comprises PEG4000.

Embodiment 13

A medical article formed from a polyurethane-based resin, which is areaction product of the following ingredients: a diisocyanate; a diolchain extender; a polyglycol; and a modifying oligomer incorporated intoa backbone, as a side chain, or both of the polyurethane-based resinformed by the diisocyanate, the polyglycol, and the diol chain extender;wherein a hard segment content is in the range of from 25% to 75% byweight and a soft segment content of the resin is in the range of from75% to 25% by weight; and wherein the medical article has a contactangle with water that is 90° or greater.

Embodiment 14

The medical article of the preceding embodiment, wherein the modifyingoligomer has an alcohol (C—OH) moiety and a functional moiety.

Embodiment 15

The medical article of the preceding embodiment, wherein the functionalmoiety comprises a fluoroether, a silicone, or a combination thereof.

Embodiment 16

The medical article of any of embodiment 13 to the preceding embodiment,wherein the modifying oligomer is selected from the group consisting of:a diol-containing perfluoropolyether incorporated into the backbone, amonofunctional polysiloxane incorporated as the side chain, andcombinations thereof.

Embodiment 17

The medical article of any of embodiment 13 to the preceding embodimentcomprising a concentration of the modifying oligomer of thepolyurethane-based resin at a surface of the medical article is higherthan a theoretical concentration based on uniform distribution ofingredients of the polyurethane-based resin.

Embodiment 18

The medical article of any of embodiment 13 to the preceding embodimentcomprising a coefficient of static friction that is 0.28 or less.

Embodiment 19

The medical article of any of embodiment 13 to the preceding embodimentcomprising a water sorption of 2.2% by weight or less.

Embodiment 20

The medical article of any of embodiment 13 to the preceding embodiment,which is non-hydratable.

Embodiment 21

The medical article of any of embodiment 13 to the preceding embodiment,which is effective to reduce bacterial biofilm colony formation.

Embodiment 22

The medical article of any of embodiment 13 to the preceding embodiment,wherein the polyglycol comprises a polyalkylene glycol comprising one orboth of: a polytetramethylene ether glycol and a polyethylene glycol.

Embodiment 23

A method of infusion therapy comprising: infusing a material from amedical article according to any preceding embodiment into a patient.

Embodiment 24

The method of the preceding embodiment in the presence or absence of aseparate lubricant coated on the medical article.

Embodiment 25

The method of embodiment 23 or 24 in the presence or absence of aseparate anti-fouling agent coated on the medical article.

Embodiment 26

The method of the preceding embodiment in the absence of a separateanti-fouling agent coated on the medical article, wherein the medicalarticle is effective for a reduced amount of thrombosis formation ascompared to a medial article formed from a polyurethane-based resin,which is a reaction product of the following ingredients: adiisocyanate; a diol chain extender; a polyglycol in the absence of amodifying oligomer having an alcohol (C—OH) moiety and a functionalmoiety; wherein a hard segment content is in the range of from 25% to75% by weight and a soft segment content of the resin is in the range offrom 75% to 25% by weight.

EXAMPLES Example 1

Various polyurethane resins were made in accordance with Table 1 by theone-step copolymerization process (no catalyst or solvent) using apilot-scale polyurethane (PU) processor as described earlier inaccordance with Exemplary Formulation I-C as shown above. Exemplaryformulations have MDI as an aromatic diisocyanate, a combination ofpolytetramethylene ether glycols (PTMEGs with average equivalentmolecular weight of 500-1000 Da) and optionally polyethylene glycol 4000(PEG-4000) as the polyglycol mixture, 1,4-butanediol as the chainextender, and the modifying oligomer(s) according to Table 1. Referencepolyurethanes without a modifying oligomer were made as well.

The modifying oligomers were selected from the group consisting of:dialcohol-terminated, ethoxylated perfluoropolyether (PFPE) (Fluorolink®E10-H) and monodialcohol-terminated polydimethylsiloxane (PDMS)(MCR-C62), and combinations thereof. Examples 1-A to 1-H are“mono-functional,” incorporating only one modifying oligomer. Examples1-I to 1-K are “bi-functional,” incorporating two modifying oligomers.Examples 1-L to 1-N are references without modifying oligomers.

TABLE 1 HARD LOCATION OF SEGMENT MODIFYING MODIFYING EXAMPLE CONTENTOLIGOMER OLIGOMER SOFT SEGMENT CONTENT 1-A 61.0 wt. % Fluorolink ® E10-HBackbone 1.77 wt. % of Fluorolink ® E10-H 37.23 wt. % of PTMEG 1-B-I61.0 wt. % Fluorolink ® E10-H Backbone 3.55 wt. % of Fluorolink ® E10-H35.45 wt. % of PTMEG 1-B-II 61.0 wt. % Fluorolink ® E10-H Backbone 3.55wt. % of Fluorolink ® E10-H 35.45 wt. % of PTMEG 1-C 61.0 wt. %Fluorolink ® E10-H Backbone 7.11 wt. % of Fluorolink ® E10-H 31.89 wt. %of PTMEG 1-D 61.0 wt. % Fluorolink ® E10-H Backbone 1.77 wt. % ofFluorolink ® E10-H 1.77 wt. % of PEG-4000 35.46 wt. % of PTMEG 1-E 61.0wt. % MCR-C62 Side Chain 1.77 wt. % of MCR-C62 37.23 wt. % of PTMEG1-F-I 61.0 wt. % MCR-C62 Side Chain 3.55 wt. % of MCR-C62 35.45 wt. % ofPTMEG 1-F-II 61.0 wt. % MCR-C62 Side Chain 3.55 wt. % of MCR-C62 35.45wt. % of PTMEG 1-G 61.0 wt. % MCR-C62 Side Chain 7.11 wt. % of MCR-C6231.89 wt. % of PTMEG 1-H 61.0 wt. % MCR-C62 Side Chain 1.77 wt. % ofMCR-C62 1.77 wt. % of PEG-4000 35.46 wt. % of PTMEG 1-I 61.0 wt. %Fluorolink ® E10-H Backbone 1.18 wt. % of Fluorolink ® E10-H MCR-C62Side Chain 1.18 wt. % of MCR-C62 36.64 wt. % of PTMEG 1-J 61.0 wt. %Fluorolink ® E10-H Backbone 1.18 wt. % of Fluorolink ® E10-H MCR-C62Side Chain 1.18 wt. % of MCR-C62 1.18 wt. % of PEG-4000 35.46 wt. % ofPTMEG 1-K 61.0 wt. % Fluorolink ® E10-H Backbone 1.77 wt. % ofFluorolink ® E10-H MCR-C62 Side Chain 1.77 wt. % of MCR-C62 35.46 wt. %of PTMEG 1-L 61.0 wt. % NONE — 39.0 wt. % of PTMEG REFERENCE 1-M 61.0wt. % NONE — 1.77 wt. % of PEG-4000 REFERENCE 37.23 wt. % of PTMEG 1-N61.0 wt. % NONE — 3.55 wt. % of PEG-4000 REFERENCE 35.45 wt. % of PTMEG

Examples 1-B-I and 1-B-II have the same overall material composition. PU1-B-I was prepared by direct copolymerization while PU 1-B-II wasprepared by uniform blending/compounding of two different PUs (i.e.,50/50 wt. % blend of PUs 1-C and reference 1-L). Similarly, Examples1-F-I and 1-F-II have the same overall material composition. PU 1-F-Iwas prepared by direct copolymerization while PU 1-F-II was prepared byblending/compounding (i.e., 50/50 wt. % blend of PUs 1-G and reference1-L).

Table 2 shows gel temperatures and gel times for the copolymerizationreactions according to Examples 1-B-I, 1-C, 1-F-I, 1-G, reference 1-L,and reference 1-N.

TABLE 2 EXAMPLE Gel temperature (° C.) Gel time (second) 1-B-I 166 50.91-C 176 47.4 1-F-I 163 49.2 1-G 181 48.9 1-L 170 54.8 REFERENCE 1-N 16649.9 REFERENCE

Incorporation of a modifying oligomer during copolymerization did notreduce the overall reactivity of the reaction system. Thecopolymerization reactions of the inventive polyurethane resinsproceeded as fast as the reference PU resins.

Example 2

Testing

For each example of Table 1, Polyurethane (PU) slabs (dimension of about7.7 in×3.5 in×0.3 in) were produced from the above mentioned pilot-scalePU processor and conveyor oven curing system, which were subsequentlygrinded into granulated forms and extruded into ribbon sheets formaterial physical property characterizations. The thickness of theribbon sheets was 0.004-0.008 in.

Tensile Property Testing. Tensile properties of both the reference andthe inventive PU ribbons (thickness of 0.004-0.008 in.) werecharacterized using Instron. The testing was performed at roomconditions (23° C., 50% RH, and >40 h equilibration time), which isprovided in Table 3 (mean of 10 measurements for each data).

TABLE 3 Tensile at break (psi) Tensile at Tensile at — Tensile atTensile at Tensile at 100% 200% Young's Elongation 5% strain 25% strain50% strain strain strain Modulus EXAMPLE at break (%) (psi) (psi) (psi)(psi) (psi) (MPa) 1-A 9335.87 2488.68 2453.85 2771.02 3643.60 5950.87575.11 — 305.24 1-B-I 10431.46 3061.65 2835.57 3060.35 3852.15 6025.31681.88 — 348.21 1-B-II 11723.70 3136.57 2752.06 2970.45 3954.10 6769.87738.48 — 323.62 1-C 9107.09 3728.87 2737.82 2786.26 3560.44 5996.42866.97 — 293.95 1-D 9335.29 2475.80 2630.55 2874.52 3553.76 5417.62538.06 — 360.35 1-E 10001.34 2754.85 2557.02 2832.88 3808.26 6523.15643.59 — 292.44 1-F-I 9931.10 3062.44 2627.61 2817.42 3646.86 6202.49681.71 — 307.76 1-F-II 10710.55 3326.33 2660.70 2863.57 3800.39 6530.99762.95 — 308.63 1-H 10055.40 2648.25 2647.55 2925.06 3708.15 5852.68596.74 — 341.44 1-I 11648.80 2968.35 2722.92 3006.75 3983.96 6629.36684.66 — 333.57 1-J 9720.48 2675.00 2654.75 2920.36 3723.50 5877.22590.67 — 329.62 1-K 10260.23 3146.99 2795.14 3031.32 3893.26 6475.68696.93 — 308.77 1-L 11003.46 2317.78 2537.44 2904.74 3932.39 6707.76528.77 REFERENCE — 306.27 1-M 10771.98 2098.89 2456.02 2851.97 3775.586142.58 476.41 REFERENCE — 338.51 1-N 8359.43 2065.87 2397.94 2641.153273.58 4995.22 435.13 REFERENCE — 355.94

Testing was also performed at body indwell conditions (37° C., salinesolution equilibration for 4 hours), which is provided in Table 4 (meanof 10 measurements for each data). Soften ratio is defined according tothe following Equation (1).

$\begin{matrix}{{{Soften}\mspace{14mu}{Ratio}} = {\frac{\begin{matrix}{{{{Young}'}s\mspace{14mu}{Modulus}{\mspace{11mu}\;}{at}\mspace{14mu}{Room}{\mspace{11mu}\;}{Conditions}} -} \\{{{Young}'}s\mspace{14mu}{Modulus}{\mspace{11mu}\;}{at}{\mspace{11mu}\;}{Body}\mspace{14mu}{Indwell}\mspace{14mu}{Conditions}}\end{matrix}}{{{Young}'}s\mspace{14mu}{Modulus}{\mspace{11mu}\;}{at}\mspace{14mu}{Room}\mspace{14mu}{Conditions}} \times 100\%}} & {{Equation}\mspace{14mu}(1)}\end{matrix}$

TABLE 4 Tensile at break (psi) Tensile Tensile Tensile Tensile Tensile —at 5% at 25% at 50% at 100% at 200% Young's Soften Elongation strainstrain strain strain strain Modulus Ratio EXAMPLE at break (%) (psi)(psi) (psi) (psi) (psi) (MPa) (%) 1-A 9534.19 514.41 1031.70 1243.581665.79 3444.07 92.53 83.91 — 388.18 1-B-I 9326.23 650.83 1223.771399.75 1781.23 3314.68 109.40 83.96 — 435.48 1-B-II 10475.36 566.441118.45 1392.06 2005.20 4130.25 104.77 85.81 — 368.03 1-C 8676.21 723.791235.77 1467.23 1961.91 3757.50 140.23 83.83 — 365.53 1-D 7356.43 521.141089.67 1230.13 1512.84 2715.69 92.05 82.89 — 436.90 1-E 9793.78 466.94993.37 1255.29 1793.56 3916.68 85.59 86.70 — 348.66 1-F-I 8929.89 536.551049.22 1272.20 1770.41 3624.96 98.63 85.53 — 362.25 1-F-II 9145.75539.28 1058.57 1318.56 1920.58 3928.11 95.64 87.46 — 350.18 1-H 8870.28582.27 1104.33 1277.61 1657.98 3169.39 105.36 82.34 — 414.18 1-I10135.94 552.58 1093.60 1331.49 1835.61 3820.71 100.69 85.29 — 372.621-J 8709.39 613.74 1137.38 1314.39 1716.58 3281.68 112.83 80.90 — 400.951-K 10813.34 583.37 1201.74 1439.83 1928.56 3749.18 94.87 86.39 — 412.761-L 9500.22 408.47 992.86 1268.98 1820.49 3970.41 62.66 88.15 REFERENCE— 343.55 1-M 8544.77 481.76 1000.01 1182.88 1544.04 3041.71 82.04 82.78REFERENCE — 395.76 1-N 6286.08 511.56 1025.95 1142.83 1379.75 2399.1785.19 80.42 REFERENCE — 431.58

Data in Tables 3 and 4 show that inventive PUs 1-B-I and 1-B-II (sameoverall material composition, where PU 1-B-I was a single target PUcomposition and PU 1-B-II was a blend of two different PUs, i.e., 50/50wt. % blend of PUs 1-C and reference 1-L) exhibited comparable tensileproperties. Similarly, inventive PUs 1-F-I and 1-F-II exhibitedcomparable tensile properties.

By comparison of tensile properties of reference PUs 1-L, 1-M and 1-Nboth at room conditions and body indwell conditions, with increase ofPEG-4000 content in PTMEG soft segment, material tensile at breakdecreased while material elongation at break increased; material Young'smodulus at room conditions decreased while material Young's modulus atbody indwell conditions increased, resulting in reduced soften ratio asdefined in Equation (1). Similar trend can be observed by comparison ofinventive PUs 1-A vs. 1-D, 1-E vs. 1-H and 1-I vs. 1-J.

Comparison of tensile properties of reference PU 1-L with inventive PUs1-A, 1-B and 1-C both at room conditions and body indwell conditionsshows that with introduction of modifying oligomer Fluorolink® E10-H,material tensile at break and elongation at break did not changesignificantly. However, with increase of modifying oligomer Fluorolink®E10-H content, material Young's modulus both at room conditions and bodyindwell conditions increased. Similar trend can be observed bycomparison of reference PU 1-M with inventive PU 1-D.

Comparison of tensile properties of reference PU 1-L with inventive PUs1-E and 1-F both at room conditions and body indwell conditions showsthat with introduction of modifying oligomer MCR-C62, material tensileat break and elongation at break did not change significantly. However,with increase of modifying oligomer MCR-C62 content, material Young'smodulus both at room conditions and body indwell conditions increased.Similar trend can be observed by comparison of reference PU 1-M withinventive PU 1-H.

Comparison of tensile properties of reference PU 1-L with inventive PUs1-I and 1-K both at room conditions and body indwell conditions showsthat with introduction of modifying oligomers Fluorolink® E10-H andMCR-C62, material tensile at break and elongation at break did notchange significantly, but material Young's modulus both at roomconditions and body indwell conditions increased.

Overall, after introduction of modifying oligomers Fluorolink® E10-Hand/or MCR-C62, the inventive novel PUs exhibited desirable tensileproperties for medical device applications.

X-Ray Photoelectron Spectroscopy (XPS) Surface Analysis.

Surface elemental analysis of both the reference and the inventive PUribbons were characterized using Fisons Surface Science SSX-100 Model206 ESCA/XPS Spectrometer. The X-ray source is monochromatic Al K-alpharadiation with photon energy of 1486.6 eV; electrons have a take-offangle of 35°, detecting surface depth of 6-7 nm. The PU ribbons weresurface-cleaned with 70% IPA/30% de-ionized water and then annealed at95° C. for 2 hours prior to XPS surface analysis. Table 5 showselemental wt. % calculated based on material bulk composition incomparison with elemental wt. % based on XPS ribbon surface analysis(mean of 6 measurements for each data). XPS technique does not analyzehydrogen, thus hydrogen was also omitted in bulk compositioncalculation.

TABLE 5 Elemental wt. % calculated Elemental wt. % based on XPS based onbulk composition (%) ribbon surface analysis (%) EXAMPLE C O N F Si C ON F Si 1-A 71.62 21.43 5.86 1.09 N/A 49.77 19.84 2.27 28.12 N/A 1-B-I70.70 21.28 5.84 2.18 N/A 38.17 18.86 1.59 41.38 N/A 1-B-II 70.70 21.285.84 2.18 N/A 42.83 18.94 2.21 36.02 N/A 1-C 68.85 21.00 5.79 4.36 N/A36.74 17.79 1.58 43.89 N/A 1-D 71.37 21.69 5.85 1.09 N/A 43.75 20.121.93 34.21 N/A 1-E 71.89 21.55 5.86 N/A 0.70 59.39 21.94 1.48 N/A 17.191-F-I 71.24 21.52 5.85 N/A 1.39 48.85 23.33 0.82 N/A 27.00 1-F-II 71.2421.52 5.85 N/A 1.39 51.34 21.95 0.84 N/A 25.87 1-H 71.64 21.81 5.85 N/A0.70 57.63 23.52 1.39 N/A 17.47 1-I 71.49 21.46 5.86 0.73 0.46 45.2021.00 1.70 23.02  9.08 1-J 71.33 21.64 5.85 0.73 0.46 43.34 21.05 1.3023.10 11.20 1-K 70.97 21.40 5.84 1.09 0.70 42.94 21.00 1.29 22.18 12.601-L 72.54 21.57 5.88 N/A N/A 73.66 24.98 1.36 N/A N/A REFERENCE 1-M72.29 21.84 5.87 N/A N/A 75.20 22.48 2.32 N/A N/A REFERENCE 1-N 72.0422.11 5.85 N/A N/A 72.34 26.56 1.10 N/A N/A REFERENCE

Data in Table 5 show that inventive PUs 1-B-I and 1-B-II (same overallmaterial composition, where PU 1-B-I was a single target PU compositionand PU 1-B-II was a blend of two different PUs) exhibited comparablesurface elemental contents. Similarly, inventive PUs 1-F-I and 1-F-IIexhibited comparable surface elemental contents.

Based on XPS surface analysis of reference PUs 1-L, 1-M and 1-N, thereis a higher concentration of polyglycol-based soft segment (proved byhigher oxygen content) on the surface than its theoretical value and alower concentration of urethane hard segment (proved by lower nitrogencontent) on the surface than its theoretical value, due to the phaseseparation of soft and hard segments within PUs.

Based on XPS surface analysis of inventive PUs 1-A, 1-B and 1-C, thereis a significantly higher concentration of Fluorolink® E10-H softsegment (proved by significantly higher fluorine content) on the surfacethan its theoretical value. It is worthwhile to point out that with 100%of Fluorolink® E10-H based PU chemistry on the surface, the maximumpotential fluorine content based on XPS analysis (excluding hydrogen)should be 50.94 wt. %. Table 5 shows that introduction of only 1.77 wt.% of Fluorolink® E10-H (Example 1-A) gave a surface fluorine content of28.12 wt. %; introduction of only 3.55 wt. % of Fluorolink® E10-H(Example 1-B) gave a surface fluorine content of 41.38 wt. %, which hasbeen close to its maximum theoretical value; further increase ofFluorolink® E10-H content to 7.11 wt. % (Example 1-C) only slightlyincreased the surface fluorine content to 43.89 wt. %. Thus we canconclude that introduction of less than 10 wt. % of Fluorolink® E10-Hhas been adequate to maximize the resulting PU surface property;introduction of higher than 10 wt. % of Fluorolink® E10-H modifyingoligomer would not provide benefits in terms of surface propertymodification. Without intending to be bound by theory, such highfluorine content on material surface would improve its surfaceproperties (hydrophobic, lubricious and/or antifouling).

Based on XPS surface analysis of inventive PUs 1-E and 1-F, there is asignificantly higher concentration of MCR-C62 soft segment (proved bysignificantly higher silicon content) on the surface than itstheoretical value. It is worthwhile to point out that with 100% ofMCR-C62 based PU chemistry on the surface, the maximum potential siliconcontent based on XPS analysis (excluding hydrogen) should be 37.58 wt.%. Table 5 shows that introduction of only 1.77 wt. % of MCR-C62(Example 1-E) gave a surface silicon content of 17.19 wt. %;introduction of only 3.55 wt. % of MCR-C62 (Example 1-F) gave a surfacesilicon content of 27.00 wt. %, which has been close to its maximumtheoretical value. Thus we can conclude that similar to Fluorolink®E10-H, introduction of less than 10 wt. % of MCR-C62 has been adequateto maximize the resulting PU surface property; introduction of higherthan 10 wt. % of MCR-C62 modifying oligomer would not provide benefitsin terms of surface property modification. Without intending to be boundby theory, such high silicon content on material surface would improveits surface properties (hydrophobic, lubricious and/or antifouling).

Based on XPS surface analysis of inventive PUs 1-I and 1-K, there aresignificantly higher concentrations of Fluorolink® E10-H and MCR-C62soft segments (proved by significantly higher fluorine and siliconcontents) on the surface than their theoretical values. Table 5 showsthat introduction of only 1.18 wt. % of Fluorolink® E10-H and 1.18 wt. %of MCR-C62 (Example 1-I) gave a surface fluorine content of 23.02 wt. %and silicon content of 9.08 wt. %; further increase of both Fluorolink®E10-H and MCR-C62 contents to 1.77 wt. % (Example 1-K) did not furtherincrease the surface fluorine content and only slightly increased thesurface silicon content to 12.60 wt. %. Thus we can conclude thatintroduction of less than 10 wt. % in total of Fluorolink® E10-H andMCR-C62 has been adequate to maximize the resulting PU surface property;introduction of higher than 10 wt. % in total of Fluorolink® E10-H andMCR-C62 modifying oligomers would not provide benefits in terms ofsurface property modification. Without intending to be bound by theory,such high fluorine and silicon contents on material surface wouldimprove its surface properties (hydrophobic, lubricious and/orantifouling).

Based on XPS surface analysis of inventive PUs 1-A and 1-D, introductionof PEG-4000 in replace of original PTMEG soft segment could promoteFluorolink® E10-H migration onto surface. Table 5 shows that originalExample 1-A has a surface fluorine content of 28.12 wt. %; however,Example 1-D (with 1.77 wt. % of PEG-4000 introduction) has a highersurface fluorine content of 34.21 wt. %. This is presumably due to theincreased segment phase separation as Fluorolink® E10-H is hydrophobicand PEG-4000 is more hydrophilic than PTMEG. Similar trend can beobserved by comparison of inventive PUs 1-E vs. 1-H and 1-I vs. 1-J, asMCR-C62 is also hydrophobic.

In addition, inventive PU ribbon examples 1-A to 1-K are much lesstransparent (white cloudy) compared to the reference PU ribbon examples1-L to 1-N. Without intending to be bound by theory, this is likely dueto the increased copolymer phase separation within the inventive PFPE-and/or PDMS-containing PUs by introduction of Fluorolink® E10-H and/orMCR-C62, which could consequently affect light scattering. Thisincreased copolymer phase separation has been discussed with respect toXPS analysis above. Even though white cloudy, the inventive PFPE- and/orPDMS-containing PU ribbon examples 1-A to 1-K still show adequatetransparency to see through for blood flashback identification when usedfor catheter tubing applications.

Coefficient of Static Friction.

A Coefficient of Friction Tester Model 32-25 was used for this testing.Coefficient of static friction was determined by measuring the angle atwhich the metal block surface began to slide against the reference andinventive PU ribbon surfaces as the incline was increased at a constantrate. The coefficient of static friction is numerically equivalent tothe tangent of that angle, which is provided in Table 6 (mean of 15measurements for each data).

TABLE 6 EXAMPLE COEFFICIENT OF STATIC FRICTION 1-A 0.2847 1-B-I 0.26771-C 0.2277 1-D 0.2721 1-E 0.1977 1-F-I 0.2186 1-F-II 0.2314 1-H 0.23321-J 0.2471 1-K 0.2152 1-L REFERENCE 0.2828

Data in Table 6 show that inventive PUs 1-F-I and 1-F-II (same overallmaterial composition, where PU 1-F-I was a single target PU compositionand PU 1-F-II was a blend of two different PUs) exhibited comparablesurface coefficient of static friction.

Table 6 shows that introduction of 1.77 wt. % and even 3.55 wt. % ofmodifying oligomer Fluorolink® E10-H did not significantly change thematerial surface coefficient of static friction; however, introductionof 7.11 wt. % of modifying oligomer Fluorolink® E10-H (Example 1-C)reduced the material surface coefficient of static friction from 0.2828down to 0.2277. On the other hand, introduction of only 1.77 wt. % ofmodifying oligomer MCR-C62 has been adequate to reduce material surfacecoefficient of static friction down to the level of around 0.2. Thus,both of the modifying oligomers Fluorolink® E10-H and MCR-C62 canprovide lubricious surface property, but MCR-C62 is a more efficientmodifying oligomer in this case. Overall, less than 10 wt. % in total ofFluorolink® E10-H and MCR-C62 has been adequate to maximize theresulting PU surface property.

Water Contact Angle.

The reference and inventive PU ribbons were surface-cleaned with 70%IPA/30% de-ionized water and then annealed at 95° C. for 2 hours priorto water contact angle measurement. Table 7 shows the water contactangle data (mean of 10 measurements for each data).

TABLE 7 EXAMPLE CONTACT ANGLE (°) 1-A 90.7 1-B-I 92.7 1-B-II 95.1 1-C101.2 1-D 90.3 1-E 96.7 1-F-II 92.6 1-I 92.7 1-J 90.8 1-K 91.7 1-LREFERENCE 77.0 1-N REFERENCE 81.2

Data in Table 7 show that inventive PUs 1-B-I and 1-B-II (same overallmaterial composition, where PU 1-B-I was a single target PU compositionand PU 1-B-II was a blend of two different PUs) exhibited comparablesurface contact angle.

Table 7 shows that introduction of modifying oligomer Fluorolink® E10-Hresulted in increased contact angle as the modified PU surface becamemore hydrophobic; with increase of modifying oligomer Fluorolink® E10-Hcontent, contact angle (surface hydrophobicity) increased. Similarly,introduction of modifying oligomer MCR-C62 or both Fluorolink® E10-H andMCR-C62 also resulted in more hydrophobic PU surface and increasedcontact angle.

Water Sorption.

The reference and inventive PU ribbons went through the followingprocedures for water sorption measurements: (i) cut ribbons (5replicates for each group of ribbon material) into rectangular shape(around 1.4 in. length and 0.51 in. width); (ii) dried all sample ribboncuts in an oven at 95° C. overnight; (iii) weighed each dry ribbon cut;(iv) submerged each dry ribbon cut into 37° C. de-ionized water for 4 h;(v) immediately after taking the ribbon cut out of water, used a tissuepaper to wipe off the surface free water and re-weighed the saturatedribbon cut; (vi) recorded all the pre-hydration and post-hydrationweight data and calculated water sorption based on the followingEquation (2).

$\begin{matrix}{{{Water}\mspace{14mu}{Sorption}} = {\frac{\begin{matrix}{{{Post}\mspace{14mu}{Hydration}\mspace{14mu}{Sample}\mspace{14mu}{Weight}} -} \\{{Dry}\mspace{14mu}{Sample}{\mspace{11mu}\;}{Weight}}\end{matrix}}{{Dry}\mspace{14mu}{Sample}\mspace{14mu}{Weigth}} \times 100\%}} & {{Equation}\mspace{14mu}(2)}\end{matrix}$Table 8 shows the water sorption data (mean of 5 measurements for eachdata).

TABLE 8 EXAMPLE WATER SORPTION (%) 1-A 1.86 1-B-II 1.74 1-C 1.83 1-D2.04 1-E 1.93 1-F-I 1.78 1-F-II 1.81 1-H 2.10 1-J 1.75 1-K 1.93 1-LREFERENCE 2.28 1-N REFERENCE 2.73

Data in Table 8 show that inventive PUs 1-F-I and 1-F-II (same overallmaterial composition, where PU 1-F-I was a single target PU compositionand PU 1-F-II was a blend of two different PUs) exhibited comparablewater sorption.

Comparison of water sorption of reference PUs 1-L and 1-N, shows thatintroduction of PEG-4000 in replace of PTMEG soft segment resulted inincreased water sorption of PU material. This is consistent withPEG-4000 is more hydrophilic than PTMEG. Similar trend can be observedby comparison of inventive PUs 1-A vs. 1-D and 1-E vs. 1-H.

Table 8 also shows that introduction of modifying oligomer Fluorolink®E10-H and/or MCR-C62 resulted in reduced water sorption due tohydrophobic property of Fluorolink® E10-H as well as MCR-C62.

Hydratability.

The reference and inventive PU ribbons went through the followingprocedures for hydratability measurements: (i) cut ribbons (5 replicatesfor each group of ribbon material) into rectangular shape (around 1.4in. length and 0.51 in. width); (ii) measured the dimensions (length andwidth) of each ribbon cut; (iii) submerged each ribbon cut into 37° C.saline solution for 4 h; (iv) immediately after taking the ribbon cutout of saline solution, re-measured the dimensions (length and width) ofeach saturated ribbon cut; (v) recorded all the pre-hydration andpost-hydration dimension data and calculated dimension changes based onthe following Equation (3).

$\begin{matrix}{{{Dimension}\mspace{14mu}{Change}} = {\frac{\begin{matrix}{{{Post}\mspace{14mu}{Hydration}\mspace{14mu}{Sample}\mspace{14mu}{Dimension}} -} \\{{Original}{\mspace{11mu}\;}{Sample}\mspace{14mu}{Dimension}}\end{matrix}}{{Original}\mspace{14mu}{Sample}\mspace{14mu}{Dimension}} \times 100\%}} & {{Equation}\mspace{14mu}(3)}\end{matrix}$

Table 9 shows the dimension change data (mean of 5 measurements for eachdata).

TABLE 9 Dimension Change - Dimension Change - EXAMPLE Length (%) Width(%) 1-B-I 0.58 0.57 1-D 0.42 0.37 1-F-I 0.38 0.36 1-H 0.24 0.43 1-J 0.350.22 1-K 0.44 0.27 1-L REFERENCE 0.43 0.17 1-N REFERENCE 0.64 0.50

Table 9 shows that both the reference and inventive PU ribbons exhibiteddimension changes of less than 1% after hydration. Thus, all these PUmaterials are dimensionally stable upon hydration and can be categorizedas non-hydratable materials.

Thermogravimetric Analysis (TGA).

The reference and inventive PU granulates/chips were analyzed using TAInstruments TGA Q500. For testing, 3 mg of each sample was heated from25° C. to 800° C. at 10° C./min in Nitrogen gas. Table 10 shows thedegradation temperatures (based on 1% and 5% weight losses) of both thereference and inventive PU materials.

TABLE 10 Degradation T at 1% of Degradation T at 5% of EXAMPLE WeightLoss (° C.) Weight Loss (° C.) 1-B-I 266.8 299.6 1-C 266.7 296.0 1-F-I275.9 304.6 1-G 278.0 303.1 1-L REFERENCE 263.2 295.9 1-N REFERENCE265.4 299.0

Table 10 shows that introduction of modifying oligomer Fluorolink® E10-Hdid not change thermal property of the resulting PU significantly;introduction of modifying oligomer MCR-C62 resulted in around 10° C.increase of the degradation temperature.

FIG. 1 shows an example of the TGA scan for the inventive PU 1-B-I.

Differential Scanning Calorimetry (DSC).

The reference and inventive PU granulates/chips were analyzed using TAInstruments DSC Q2000. For testing, 5 mg of each sample was used forheat/cool/heat cycles; Cycle 1=heat from 25° C. to 250° C. at 10°C./min; Cycle 2=cool from 250° C. to −50° C. at 10° C./min; Cycle 3=heatfrom −50° C. to 250° C. at 10° C./min. Table 11 shows the glasstransition temperature (T_(g), onset from heating Cycle 3),crystallization temperature (T_(c), peak from cooling Cycle 2), meltingtemperature onset from heating Cycle 1 (T_(m1)), and melting temperatureonset from heating Cycle 3 (T_(m2)) of both the reference and inventivePU materials.

TABLE 11 T_(g) (onsite T_(c) (peak T_(m1) (onsite T_(m2) (onsite fromfrom from from heating cooling heating heating Cycle 3) Cycle 2)Cycle 1) Cycle 3) EXAMPLE ° C. ° C. ° C. ° C. 1-B-I −1.4 146.8 & 113.3207.5 192.1 1-C 1.5 135.8 & 108.1 212.2 193.5 1-F-I 14.5 98.5 208.3132.5 1-G 13.2 111.2 193.5 152.9 1-L 10.8 84.8 135.1 124.4 REFERENCE 1-N3.4 105.0 160.0 152.3 REFERENCE

Fluorolink® E10-H modified PUs 1-B-I and 1-C showed two separate peaksin cooling Cycle 2, thus two individual T_(c) are identified in Table11; MCR-C62 modified PUs 1-F-I and 1-G showed a larger difference ofT_(m) based on heating Cycle 1 vs. heating Cycle 3; for T_(m) endotherm,more than one endothermic transition were overlapped in some cases,which might be attributed to the disruption/dissociation of domains withshort/long range orders as well as melting of microcrystallites of thehard segments. It is hard to completely differentiate these endothermictransitions individually, thus they were all combined together foranalysis and only one onsite T_(m) was reported as the result. Theseinformation will be useful and can be referenced for ribbon and tubingextrusion of the new inventive PU materials.

FIG. 2 is the DSC scan of Cycle 1 and Cycle 2 for the inventive PU1-B-I. FIG. 3 is the DSC scan of Cycle 3 for the inventive PU 1-B-I.

Melt Flow Index.

The reference and inventive PU granulates/chips were characterized formelt flow indexes using a Zwick/Roell extrusion plastometer. Theequipment has an extrusion barrel diameter of 9.55 mm (length of 170 mm)and a piston diameter of 9.48 mm (weight of 325 g). Five (5) g of eachpre-dried (dried at 95-110° C. for over 12 hours) sample was used toperform the test at 220° C. with 5 kg of load weight and 300 seconds ofpreheat time. Table 12 shows the melt mass flow rate, melt volume flowrate and melt density of both the reference and inventive PU materials.

TABLE 12 Melt Mass Flow Melt Volume Flow Melt Density EXAMPLE Rate (g/10min) Rate (cm³/10 min) (g/cm³) 1-B-I 36.11 34.20 1.056 1-C 10.98 10.311.065 1-F-I 10.71 10.33 1.037 1-G 109.26 105.67 1.034 1-L REFERENCE11.60 11.17 1.039 1-N REFERENCE 43.42 41.57 1.044

Table 12 shows that introduction of high density (1.69 g/cm³) modifyingoligomer Fluorolink® E10-H resulted in higher melt density of theresulting PU material; melt flow rates of Fluorolink® E10-H modified PUs1-B-I and 1-C are comparable with reference PUs 1-L and 1-N as onlybackbone type soft segments were used in these cases. Introduction of3.55 wt. % of modifying oligomer MCR-C62 (Example 1-F-I) did not changethe PU melt flow rate significantly; however, introduction of 7.11 wt. %modifying oligomer MCR-C62 (Example 1-G) resulted in significantincrease of the resulting PU melt flow rate.

Biofilm Formation.

The reference and inventive PU ribbons were surface-cleaned with 70%IPA/30% de-ionized water and then annealed at 95° C. for 2 hours;afterwards, the ribbons were sealed in sterilization bags and wentthrough a standard ethylene oxide sterilization process; the sterilizedribbon samples were used for biofilm formation testing. As shown in FIG.4 , a cylindrical transparent polycarbonate chamber with an innerdiameter of 1.25 in. and a length of 21 in. was used in the testing; thereference and inventive PU ribbons were cut into small rectangular (7 mmby 25 mm) coupons and attached to caps which, when placed on the chambersuspended the coupons in the chamber; four different ribbon materials (6replicates for each material) were tested at the same time for side byside comparison; the four different materials were placed inside thechamber at alternating positions (as shown in FIG. 4 ) for samplelocation randomization. Staphylococcus epidermidis was used as thebacterium for this testing. The testing procedures are as follows:filled bacteria/culture medium into the testing chamber which submergedall 24 testing coupons; incubated at 35° C. for 1 hour to allow bacteriato attach to coupons; gravity-fed 1500 ml of saline in 10 min to removebacteria/culture medium from the chamber and then emptied the chamber; aperistaltic pump was used to circulate the culture medium between aculture medium reservoir and the chamber at 35° C. and a high shear of1500 ml/min for 24 hours to allow biofilm formation; gravity-fed 2000 mlof saline in 13 min to remove culture medium from the chamber and thenemptied the chamber; took out the coupons and each coupon was dipped insterile saline once and then in another container of sterile saline forthree additional times; bacterial biofilms on each coupon were thenrecovered into saline solution by vortexing and sonicating; enumeratedbacterial colony counts by performing 10-fold serial dilutions; aliquotsof each dilution were then cultured by the spread plate method; afterincubation of the cultures, the plates were examined and the dilutionthat had colony counts between ˜30 to 300 were counted; using thedilution factor, the initial total number of bacterial biofilms removedfrom the coupons could be calculated.

Tables 13 and 14 show the final bacterial biofilm colony counts on thereference and inventive PU ribbon coupons (mean of 6 replicate couponsfor each material).

TABLE 13 Bacterial Biofilm Colony Colony Formation EXAMPLE Formation(CFU/Coupon) Reduction (%) 1-A 3.83 × 10⁷ 25.63 1-B-II 1.13 × 10⁷ 78.061-C 2.28 × 10⁷ 55.73 1-L REFERENCE 5.15 × 10⁷ —

TABLE 14 Bacteria Biofilm Colony Colony Formation EXAMPLE Formation(CFU/Coupon) Reduction (%) 1-F-I 1.39 × 10⁷ 50.00 1-L REFERENCE 2.78 ×10⁷ —

Data show that introduction of both modifying oligomers Fluorolink®E10-H and MCR-C62 resulted in certain reduction of bacterial biofilmcolony formation, presumably due to the hydrophobic and lubricioussurface making attachment difficult of various biological agents such asbiofilms.

Example 3

For some compositions in Table 1 (inventive PUs 1-B-I, 1-C, 1-F-I, andreference PU 1-L), polyurethane granulates/chips were extruded into 22GA standard single layer catheter tubing for further tubing propertytesting. After extrusion, the tubing was annealed at 90-95° C. for 1hour. Similar as the previous ribbon findings, the inventive PU tubingsamples 1-B-I, 1-C and 1-F-I are less transparent (cloudy) compared tothe reference PU tubing sample 1-L. As described previously, this ispresumably due to the increased copolymer phase separation within theinventive PFPE- and PDMS-modified PUs by introduction of Fluorolink®E10-H or MCR-C62, which could consequently affect light scattering.However, the inventive PFPE- and PDMS-modified PU tubing samples 1-B-I,1-C and 1-F-I still showed adequate transparency to see through forblood flashback identification when used for catheter tubingapplications.

Catheter Tubing Drag Force. The above mentioned inventive and reference22 GA PU catheter tubing samples were assembled into catheter assemblies(using catheter tubing, wedge, catheter adapter, needle and needle hub).No catheter lube was applied outside of the catheter tubing during thistesting. Catheter tubing drag force was tested using an InstronUniversal Compression Tester. Natural rubber latex with a thickness ofaround 12 mils was used as the testing film. Table 15 shows the dragforce of the inventive and reference PU catheter tubing materialsagainst the natural rubber latex film (mean of 3-5 measurements for eachdata).

TABLE 15 Catheter Tubing Drag Force EXAMPLE (gram force) 1-B-I 13.67 1-C12.74 1-F-I 10.11 1-L REFERENCE 14.23

Table 15 shows similar trends as previous testing data as shown in Table6 (coefficient of static friction). Introduction of the modifyingoligomer Fluorolink® E10-H reduced the tubing drag force, but not verysignificant; however, introduction of modifying oligomer MCR-C62 canreduce the tubing drag force much more significantly. This is consistentwith the previous conclusions of Table 6 that introduction ofFluorolink® E10-H and MCR-C62 can both provide lubricious surfaceproperty, but MCR-C62 is a more efficient modifying oligomer fromlubricity point of view.

Surface Thrombogenicity Testing.

A standard chandler loop system was used to simulate the extracorporealblood circulation. PVC tubes (¼ in. ID), partly filled with recalcifiedfresh bovine blood, were formed into re-closable loops and were rotatedat a rotation speed of 20 rpm in a temperature controlled water bath(37° C.), to simulate arterial flow conditions. In the loops, variouscatheter tubing samples (22 GA and 4 inch length, through standardethylene oxide sterilization process) were positioned to testinteractions of blood with catheter tubing materials and surfaces.Thrombogenicity testing is a key component in the development of medicaldevices intended for contact with blood. In this study, we used thechandler loop model to evaluate its capacity to detect differentialthrombogenic potential of different catheter tubing materials usingrecalcified fresh bovine blood.

FIG. 5 is an annotated photograph showing thrombosis formationcomparison of the inventive PU tubing materials 1-B-I and 1-F-I vs. thereference PU tubing material 1-L using chandler loop system with highheparin concentration of 1 unit/ml and testing time of 2 hr. FIG. 5clearly shows that among these three materials, the inventive PU tubingmaterial 1-B-I (introduction of 3.55 wt. % of modifying oligomerFluorolink® E10-H) exhibited the best non-thrombogenic property; theinventive PU tubing material 1-F-I (introduction of 3.55 wt. % ofmodifying oligomer MCR-C62) exhibited relatively more thrombosisformation compared to the tubing material 1-B-I, but still better thanthe reference PU tubing material 1-L.

FIG. 6 shows thrombosis formation comparison of the inventive PU tubingmaterials 1-B-I and 1-F-I vs. the reference PU tubing material 1-L usingchandler loop system with low heparin concentration of 0.2 unit/ml andtesting time of 2 hr. FIG. 6 again shows that among these threematerials, the inventive PU tubing material 1-B-I (introduction of 3.55wt. % of modifying oligomer Fluorolink® E10-H) exhibited the bestnon-thrombogenic property; the inventive PU tubing material 1-F-I(introduction of 3.55 wt. % of modifying oligomer MCR-C62) could not bedifferentiated from the reference PU tubing material 1-L at such lowheparin concentration.

Reference throughout this specification to “one embodiment,” “certainembodiments,” “one or more embodiments” or “an embodiment” means that aparticular feature, structure, material, or characteristic described inconnection with the embodiment is included in at least one embodiment ofthe invention. Thus, the appearances of the phrases such as “in one ormore embodiments,” “in certain embodiments,” “in one embodiment” or “inan embodiment” in various places throughout this specification are notnecessarily referring to the same embodiment of the invention.Furthermore, the particular features, structures, materials, orcharacteristics may be combined in any suitable manner in one or moreembodiments.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It will be apparent to those skilled in the art thatvarious modifications and variations can be made to the method andapparatus of the present invention without departing from the spirit andscope of the invention. Thus, it is intended that the present inventioninclude modifications and variations that are within the scope of theappended claims and their equivalents.

What is claimed is:
 1. A medical article formed from apolyurethane-based resin, which is a reaction product of the followingingredients: a diisocyanate; a diol chain extender; a polyglycol; and amodifying oligomer incorporated into a backbone, as a side chain, orboth of the polyurethane-based resin formed by the diisocyanate, thepolyglycol, and the diol chain extender, the modifying oligomercomprising a diol-containing perfluoropolyether incorporated into thebackbone, the diol-containing perfluoropolyether having a structure ofHO(CH₂CH₂O)_(p)CH₂CF₂O(CF₂CF₂O)_(q)(CF₂O)_(r)CF₂CH₂(OCH₂CH₂)_(p)OHwherein p+q+r provide a fluorine content in a range of 55% to 60% byweight and the average molecular weight of the modifying oligomer is inthe range of 1500 to 2200 g/mol; wherein a hard segment content is inthe range of from 25% to 75% by weight and a soft segment content of theresin is in the range of from 75% to 25% by weight; and wherein themedical article is effective as a self-lubricating and/orself-anti-fouling medical article.
 2. The medical article of claim 1,wherein a concentration of the modifying oligomer of thepolyurethane-based resin at a surface of the medical article is higherthan a theoretical concentration based on uniform distribution ofingredients of the polyurethane-based resin.
 3. The medical article ofclaim 1, wherein the modifying oligomer further comprises amonofunctional polysiloxane incorporated as the side chain, andcombinations thereof.
 4. The medical article of claim 1, wherein themodifying oligomer is present in an amount ranging from about 0.1 toabout 10 weight percent of the overall composition of thepolyurethane-based resin.
 5. The medical article of claim 1, wherein thediisocyanate is selected from the group consisting of: an aliphaticdiisocyanate, alicyclic diisocyanate, and an aromatic diisocyanate. 6.The medical article of claim 5, wherein the diisocyanate is selectedfrom the group consisting of: 4,4′-diphenylmethane diisocyanate (MDI),toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), andmethylene-bis(4-cyclohexylisocyanate) (HMDI), and combinations thereof.7. The medical article of claim 1, wherein the diol chain extender isselected from the group consisting of: ethylene glycol, 1,3-propyleneglycol, 1,4-butanediol, neopentyl glycol, and alicyclic glycols havingup to 10 carbon atoms.
 8. The medical article of claim 1, wherein thepolyglycol is selected from the group consisting of: polyalkyleneglycol, polyester glycol, polycarbonate glycol, and combinationsthereof.
 9. The medical article of claim 1, wherein the polyglycolcomprises the polyalkylene glycol.
 10. The medical article of claim 1,wherein the polyalkylene glycol comprises one or both of: apolytetramethylene ether glycol and a polyethylene glycol.
 11. Themedical article of claim 1, wherein the polyalkylene glycol comprises apolytetramethylene ether glycol, and a polyethylene glycol thatcomprises PEG4000.
 12. A method of infusion therapy comprising: infusinga material from a medical article according to claim 1 into a patient.13. The method of claim 12, further comprising a separate lubricantcoated on the medical article.
 14. The method of claim 12, furthercomprising a separate antifouling agent coated on the medical article.15. The method of claim 14, wherein the medical article is effective fora reduced amount of thrombosis formation as compared to a medial articleformed from a polyurethane-based resin, which is a reaction product ofthe following ingredients: a diisocyanate; a diol chain extender; apolyglycol in the absence of a modifying oligomer having an alcohol(C—OH) moiety and a functional moiety; wherein a hard segment content isin the range of from 25% to 75% by weight and a soft segment content ofthe resin is in the range of from 75% to 25% by weight.